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Allogeneic Haematopoietic Stem Cell Transplant (HSCT) Is a Treatment Option That Has the Potential to Correct the Genetic Deficiency in β-Thalassaemia1,2,3

Allogeneic Haematopoietic Stem Cell Transplant (HSCT) Is a Treatment Option That Can Potentially Correct the Genetic Deficiency in Transfusion-Dependent β-thalassaemia (TDT).1,2,3

Although potentially curative, HSCT carries risks and has primarily been used in younger patients with HLA-matched donors. The best outcomes of the procedure are observed in paediatric patients with a matched sibling donor.1,2,3,4

In a retrospective study of 1493 patients with thalassaemia major who underwent transplantation between 2000 and 2010, two-year overall survival and thalassaemia-free survival were estimated to be 88% and 81%, respectively.4

Survival Rates for 1493 HSCT Recipients With Thalassaemia 
During the Period 2000-20104

Chart showing survival rates of Allogenic Haematopoietic Stem Cell Transplant Overall Survival vs Thalassaemia-Free Survival

Adapted from Baronciani D, Angelucci E, Potschger U, et al. Hematopoietic stem cell transplantation in thalassemia: a report from the European Society for Blood and Bone Marrow Transplantation Hemoglobinopathy Registry, 2000–2010. Bone Marrow Transplant. 2016;51(4):536-541.

Overall Survival and Thalassaemia-Free Survival Rates Are 
Highest in Thalassaemia Patients With a Matched Sibling Donor4

Donor Type Overall Survival Rate(%)*
(2 years post-HSCT)
Thalassaemia-Free Survival Rate(%)*
(2 years post-HSCT)
Matched Sibling Donor (n=1061) 91 ± 0.01 83 ± 0.01
Matched Related Donor (n=127) 88 ± 0.04 78 ± 0.05
Mismatched (n=57) 68 ± 0.11 68 ± 0.11
Unrelated Donor (n=210) 77 ± 0.03 77 ± 0.03

*p<0.001

HSCT: 30 Years of Enabling 
Thalassaemia-Free Survival1

Allogeneic HSCT is a treatment option with potential to correct the genetic deficiency in TDT.1

HSCT is an accepted approach to treating TDT patients with an HLA-identical related donor or a well-matched unrelated donor. In patients for whom these are not available, the options of HLA-matched unrelated cord blood donors and HLA-mismatched related donors are being experimentally explored.1

Prior to HSCT1

Prior to HSCT, Thalassaemia International Federation (TIF) guidelines recommend the following:

  • Thorough pre-transplant evaluation with accurate iron studies, including cardiac iron/function, liver iron/function, and liver histology with assessment of fibrosis
  • Chelation treatment if needed to remove as much iron as possible (ideally, the patient has had good long-term iron control secondary to regular and effective chelation therapy)
  • Evaluation of pre-transplant endocrine dysfunction to provide a frame of reference for comparison during post-transplant follow up

Following HSCT1

After HSCT, Thalassaemia International Federation (TIF) guidelines recommend the following:

  • Close monitoring of haematological and engraftment parameters, infectious complications and graft-versus-host disease (GvHD) in the first year post-HSCT
  • Immunisation in the second year post-HSCT if there is no GvHD
  • Removal of excess iron post-HSCT provided the graft is stabilised, the patient does not have chronic GvHD and is not taking any immunosuppressive treatment
  • Long-term follow-up to monitor potential development of multi-system problems like iron overload, pubertal development and growth and endocrine deficiencies related to the primary disease
  • Follow-up and referral for patients experiencing endocrine dysfunction and infertility

Determining Transplant-Related Risk Factors 
in TDT Patients

Between 1980 and 2000, more than 1000 thalassaemia patients underwent HSCT from HLA-identical
siblings in the transplant centre of Pesaro. During this time, the Pesaro group developed a prognostic scheme
to predict transplant outcomes in patients less than 17 years of age. The three risk determinants in this
prognostic scheme were related to iron burden, and are as follows:1

  1. Lifetime quality of chelation received prior to transplantation (regular versus non-regular)
  2. Hepatomegaly (defined as more than 2 centimetres below the costal margin)
  3. Presence of liver fibrosis pre-transplant, as determined by hepatic biopsy examination

Based on these variables, patients are classified into three groups:1

black info iconTo this day, outcomes of HSCT in patients with TDT are seen to be different for each of these groups.1,5

Mortality in Patients With an HLA-Identical Sibling Donor (MSD)5

CLASS I or II

CLASS III

The Use of Donor Cells in HSCT Introduces the Risk of Potentially Life-Threatening Graft-versus-Host Disease (GvHD) and Graft Rejection4,5


  • SEVERE ACUTE GvHD (GRADE III-IV)*

    9% (whole population)
    7% (patients with HLA-matched sibling donor)

  • LIMITED CHRONIC GvHD

    15% ± 1

  • EXTENSIVE CHRONIC GvHD

    6% ± 1


*Risk within first 100 days post-HSCT  2-year risk post-HSCT  P=0.001

Chronic GvHD assessment was done in 1140 patients who survived with a functioning graft for >100 days.

Mortality Risk Increases With Age4

In patients who received an HSCT from HLA-identical sibling donors, overall survival and thalassaemia-free survival decreased with age.4


Overall Survival and Thalassaemia-Free Survival in Patients With Matched Sibling Donors (MSD)4

SWIPE OR ROTATE
 
Age
<2 years
2-<5 years
5-<10 years
10-<14 years
14-<18 years
≥18 years
P-value (for trend)
  Overall Survival Thalassaemia-Free Survival
Number of Patients Events 2-year Events 2-year
66 3 0.95 ± 0.03 4 0.93 ± 0.03
266 13 0.94 ± 0.02 32 0.86 ± 0.03
352 33 0.90 ± 0.02 52 0.83 ± 0.02
197 8 0.96 ± 0.02 24 0.86 ± 0.03
97 14 0.82 ± 0.04 20 0.74 ± 0.05
82 16 0.80 ± 0.05 18 0.76 ± 0.05
  <0.001 <0.001

Adapted from Baronciani D, Angelucci E, Potschger U, et al. Hematopoietic stem cell transplantation in thalassemia: a report from the European Society for Blood and Bone Marrow Transplantation Hemoglobinopathy Registry, 2000–2010. Bone Marrow Transplant. 2016;51(4):536-541.

quotation mark

“Showing this impact of age on transplant outcomes supports the argument that thalassaemia is a progressive disease resulting in tissue damage and that deterioration starts early in a patient’s life, even in the era of oral chelation therapy.”

D Baronciani, et al., 20164

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Many patients with TDT do not receive allogeneic HSCT due to increased risk of mortality stemming from:

Take the β-Thalassaemia Challenge

HSCT using a matched sibling donor (MSD) is associated with lower risk of:

D.

All of the above.
HSCT using an MSD is associated with decreased risk of immunological complications, including GvHD and graft rejection. It is also associated with decreased risk of mortality and improved overall survival rates. Unfortunately, only 25-30% of patients have an available MSD.1,3,4,6

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